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Abstract:

The invention relates to method for reconstructing an aortic blood
pressure waveform of a person from a peripheral blood pressure waveform
of the person comprising the steps of determining at least one
pre-selected parameter of the peripheral blood pressure waveform,
reconstructing the aortic blood pressure waveform from the peripheral
blood pressure waveform using a pressure transfer function having at
least one adjustable characteristics, wherein said adjustable
characteristics is determined using the at least one pre-selected
parameter of the peripheral blood pressure waveform. The invention
further relates to a device for reconstructing an aortic blood pressure
waveform from a peripheral blood pressure waveform and a computer program
product.

Claims:

1. A method for reconstructing an aortic blood pressure waveform of a
person from a peripheral blood pressure waveform of the person
comprising: determining at least one pre-selected parameter of the
peripheral blood pressure waveform; and reconstructing the aortic blood
pressure waveform from the peripheral blood pressure waveform using a
pressure transfer function having at least one adjustable characteristic,
wherein said adjustable characteristics determined using the at least one
pre-selected parameter of the peripheral blood pressure waveform.

3. The method according to claim 2, further comprising selecting a
resonance peak of the pressure transfer function for the adjustable
characteristic.

4. A method according to claim 3, wherein the resonance peak of the
pressure transfer function (Fpeak) is adjusted according to the following
equation: Fpeak=k*CO+const, where k is an assigned coefficient value,
and const is an assigned constant value.

5. A method according to claim 3, wherein the resonance peak of the
pressure transfer function (Fpeak) is adjusted according to one of the
following equations: Fpeak=k1*(MAP-DBP)+k2*HR-k3*Delay+const, or
Fpeak=k4*(MAP-DBP)+k5*HR+const where k1, k2, k3, k4, and k5 are assigned
coefficient values, and const is an assigned constant value.

6. The method according to claim 1, further comprising measuring the
peripheral blood pressure waveform.

7. A method according to claim 6, wherein the peripheral blood pressure
waveform is measured during an exercise of the person.

8. The method according to claim 6, wherein the peripheral blood pressure
waveform is measured non-invasively.

9. The method according to claim 1, further comprising calculating a
physiological parameter characteristic of a health condition of the
person from at least aortic blood pressure waveform data.

10. A device for reconstructing an aortic blood pressure waveform from a
peripheral blood pressure waveform comprising: a memory unit for storing
a pressure transfer function having at least one adjustable
characteristic and at least the peripheral blood pressure waveform; and a
processor arranged for: determining at least one pre-selected parameter
of the peripheral blood pressure waveform; determining the at least one
adjustable characteristic of the pressure transfer function from the at
least one pre-selected parameter of the peripheral blood pressure
waveform; and reconstructing the aortic blood pressure waveform from the
peripheral blood pressure waveform using the pressure transfer function
with the at least one adjustable characteristic.

11. A device according to claim 10, further comprising a measuring unit
for measuring the peripheral blood pressure waveform.

12. A device according to claim 11, wherein the measuring unit comprises
a finger cuff or applanation tonometry sensor.

13. A computer program product comprising instructions for causing a
processor to carry out the method according to claim 1.

Description:

FIELD

[0001] The invention relates to a method for reconstructing an aortic
blood pressure waveform from a peripheral blood pressure waveform. The
invention further relates to a device and a computer program product for
reconstructing an aortic blood pressure from a peripheral blood pressure
waveform. In particular, the invention relates to a method for
reconstructing an aortic blood pressure waveform from a peripheral blood
pressure waveform during exercise.

BACKGROUND OF THE INVENTION

[0002] The relevance of arterial blood pressure changes during exercise is
well established and it is an independent predictor of cardiovascular
morbidity and mortality. Peripheral arterial blood pressure can, for
example, be measured during exercise with per se known systems which may
be utilizing a suitable finger cuff or an applanation tonometry sensor.
However, changes in peripheral pressure during exercise are not fully
representative for changes in aortic pressure. Especially systolic
pressure measured at a peripheral artery may be overestimated to a
different extent between subjects and at increasing workloads.

[0003] The transfer of a blood pressure waveform along a vascular tree is
usually characterized by a pressure transfer function (TF) in the
frequency domain. The inverse of this TF may be used for the
reconstruction of the central pressure from a pressure wave measured at a
peripheral site. At rest and at low exercise loads, acceptable results
for reconstructed aortic blood pressure waveform may be obtained using a
fixed TF, as known from Stok et al, "Changes in finger-aorta pressure
transfer function during and after exercise", J Appl Physiology 101:
1207-1214, 2006 and from Sharman et al "Validation of a generalized
transfer function to noninvasively derived central blood pressure during
exercise", Hypertension 46: 1203-1208, 2006.

[0004] During leg exercise the aortic-to-peripheral pressure transfer
function may change. Therefore, methods for determining aortic blood
pressure which do not take such change into account may be inaccurate. In
principle, during exercise, two major changes occur in the hemodynamic
status of a subject: both heart rate and mean blood pressure increase.
The pressure transfer function used to describe waveform changes from
aortic path to a periphery, expressed in the frequency domain, comprises
a characteristic resonance peak frequency. Heart rate may have no direct
influence on pressure transfer function, whereas an increase in mean
blood pressure may change vascular diameter according to the compliance
curve of the vessel, coupled with an increase in elastic modulus. This
may have a direct effect on travel time over the arteries and on the
transfer function, whereby travel time may be reduced and the resonance
peak of the pressure transfer function may be shifted to higher
frequencies. However, during leg exercise more complicated effects may
occur due to vasoconstriction in the arm as upper arm flow may not
undergo substantial changes despite a large increase in cardiac output.
This may alter the properties of the large conduit arteries as well, but
may also change the peripheral reflection coefficient of the vessels
under study.

[0005] Due to the increase in heart rate (HR) during moderate to high
workloads harmonics of the pressure wave may also be shifted to higher
frequencies. The final result on aortic pulse pressure reconstruction
with a generalized TF becomes rather unpredictable. These effects may
reduce the applicability of a generalized transfer function (genTF). It
may not be suitable to apply a generic, not individualized transfer
function for determination of aortic blood pressure waveform from
peripheral blood pressure waveform, particularly during exercise of the
person.

[0006] An embodiment of a method for reconstructing aortic blood pressure
waveform from peripheral blood pressure waveform is known from U.S. Pat.
No. 6,647,287. In the known method a model for such reconstructing is
adjustable. Accordingly, aortic blood pressure waveforms are
reconstructed from peripheral blood pressure waveform data using
mathematical models. The models may combine analytical models of pulse
wave propagation in the cardio-vascular system with empirical models
derived from measurements taken from patients. When used to reconstruct
the aortic pressure of a given subject, the models are adjusted to the
subject's physiological state, for example, based upon ECG and other
measurements.

[0007] It is a disadvantage of the known method for reconstructing aortic
blood pressure that a considerable calculus and extensive real-time
measurements are required for enabling due adjustment of used models for
taking into consideration a physiological state of the patient.

SUMMARY OF THE INVENTION

[0008] It is an object of the invention to provide a method for
reconstructing aortic blood pressure from peripheral blood pressure
waveform which is accurate for peripheral blood waveforms taken at rest
and during exercise of a person under consideration. In particular, it is
an object of the invention to model the blood pressure transfer function
from suitable heamodynamic parameters derived from the peripheral blood
pressure waveform.

[0009] To this end the method according to the invention comprises the
steps of: [0010] determining at least one pre-selected parameter of the
peripheral blood pressure waveform; [0011] reconstructing aortic blood
pressure waveform from the peripheral blood pressure waveform using a
pressure transfer function having at least one adjustable
characteristics, wherein said adjustable characteristics is determined
using the at least one pre-selected parameter of the peripheral blood
pressure waveform.

[0012] Based on profound research data it is found that for each
individual and for each exercise level a pressure transfer function from
aorta to an extremity, for example to a finger, was different. However,
it was found that a certain number of individual parameters
characterizing a peripheral blood pressure waveform can be used as
suitable adjustors of the adjustable characteristics of the pressure
transfer function. Preferably, for the pressure transfer function a
filter is selected described by two second order filter sections, for
example a filter known from Gizdulich et al "Models of brachial to finger
pulse wave distortion and pressure decrement", Cardiovasc Res 33:
698-705, 1997. It will be appreciated that other suitable pressure
transfer functions known from the art being constructed to mathematically
express a relationship between the blood pressure waveform in the aorta
and in a peripheral artery may be used.

[0013] The pressure transfer function can be constructed in the frequency
domain. This implies that in this case one considers a waveform as a sum
of a steady part (mean blood pressure) and a pulsatile part that is
composed on sine waves for a given frequency. The transfer function thus
expresses a relationship between sine waves for a given frequency between
aorta and periphery. In general two parameters suffice to describe the
relationship: a ratio between amplitudes of the sine waves (TF modulus)
and the difference in phase (TF phase). It is found that TF modulus is in
fact a variable, which depends on a physiologic condition of an
individual and which may undergo substantial change under exercise. The
TF modulus may be characterized by a peak resonance frequency Fpeak,
which, in accordance with an aspect of the invention may be
individualized for improving accuracy of determination of aortic blood
pressure waveform from a peripheral blood pressure waveform. Fpeak thus
is found to be a suitable adjustable parameter of the pressure transfer
function.

[0014] It is found that by deducing a suitable heamodynamic parameter from
a peripheral blood pressure waveform the blood pressure transfer function
can be accurately modeled in the frequency domain.

[0015] It is further found that at least one pre-selected parameter of the
blood pressure waveform is identifiable with a reasonable degree of
confidence for use as an adjustor of the pressure transfer function. Such
at least one pre-selected parameter may be selected or derived from a
group comprising: cardiac output (CO), heart rate (HR), stroke volume
(SV), total peripheral resistance (TPR), pressure wave delay (Delay),
peripheral mean arterial pressure (MAP), diastolic arterial pressure
(DBP). Preferably, the cardiac output (CO) is derived from analysis of
the peripheral blood pressure waveform, such as using pulse contour
method (pcCO).

[0016] It is further found that the resonance peak of the pressure
transfer function can be reliably adjusted in accordance with a linear
equation:

[0018] Alternatively, it is possible to use more than one pre-selected
parameter for individually adjusting the peak resonance frequency of the
pressure transfer function. For example, the resonance peak of the
pressure transfer function is adjusted in accordance with an equation:

Fpeak=k1*(MAP-DBP)+k2*HR-k3*Delay+const1,

or

Fpeak=k4*(MAP-DBP)+k5*HR+const2,

wherein the following numerical values for the coefficients and the
constants may be assigned:

k1=0.0701;

k2=0.0193;

k3=0.131;

k4=0.0764;

k5=0.0234;

const1=2.7067;

const2=0.6478.

[0019] These coefficients and constants may be determined using regression
analysis of a suitable plurality of measured data for developing a
formula determining the frequency at which an individual TF has an
extremum, for example a peak (Fpeak). The Gizdulich filter was found
to be suitably adaptable for allowing for a peak shift in response to any
of the above equations. The combination of the thus determined
individualized peak frequency applied to a generic adaptable pressure
transfer function yields an individualized pressure transfer function TF
(indTF). It is found that by using indTF accuracy of reconstruction of
the aortic blood pressure waveform is substantially improved with respect
to results obtained with generic transfer function (genTF).

[0020] In an embodiment of the method according to the invention, a shift
in peak resonance frequency (Fpeak) of the individual
aorta-peripheral transfer function (TF) is determined during exercise.
For this purpose parameters extracted from the peripheral pressure pulse,
as mentioned above may be used. In this way a bias and scatter in the
reconstructed aorta pulse pressure present in the method known from the
art are mitigated thereby improving accuracy of determination of aortic
blood pressure waveform from peripheral measurements, in particularly,
during exercise.

[0021] It will be appreciated that determination of an aortic blood
pressure waveform from a peripheral blood pressure may take place
off-line, based on previously acquired peripheral blood pressure waveform
data. It is possible that such data is made available by means of a
suitable Hospital Information System (HIS), via internet, or,
alternatively, it may be stored locally, for example in a suitable blood
pressure measurement device.

[0022] Preferably, the method according to the invention is carried out
on-line and comprises, therefore, the step of measuring the peripheral
blood pressure waveform. More preferably peripheral blood pressure is
carried out non-invasively, for example, using a finger cuff or using
applanation tonometry. It will be appreciated that use of an invasive
measurement or a measurement on another suitable extremity is
contemplated.

[0023] In a further embodiment of the method according to the invention
the method further comprises a step of calculating a physiological
parameter characteristic of a health condition of the person from at
least reconstructed aortic blood pressure waveform data.

[0024] It is found to be particularly advantageous to use aortic pressure
data reconstructed with increased accuracy, particularly under exercise,
for determining a suitable physiological parameter characteristic of a
health condition of the individual. For example, cardiac workload in
exercise or under psychological stress may be determined and a suitable
advice may be put forward to the individual.

[0025] A device for reconstructing aortic blood pressure waveform from a
peripheral blood pressure waveform comprising: [0026] a memory unit for
storing a pressure transfer function having at least one adjustable
characteristics and at least the peripheral blood pressure waveform;
[0027] a processor arranged for [0028] determining at least one
pre-selected parameter of the peripheral blood pressure waveform; [0029]
determining the adjustable parameter of the pressure transfer function
from the at least one pre-selected parameter of the peripheral blood
pressure waveform; [0030] reconstructing of aortic blood pressure
waveform from a peripheral blood pressure using the pressure transfer
function with the adjusted characteristics.

[0031] Preferably, the device comprises a measuring unit for measuring the
peripheral blood pressure waveform. For example, either an invasive
system, or a non-invasive system may be used. Suitable example of the
latter relates to a finger cuff or applanation tonometry.

[0032] More preferably, the device according to the invention comprises a
computing unit for calculating a suitable physiological parameter
characteristic of a health condition of the individual.

[0033] Optionally, the device according to the invention may form part of
a suitable health monitoring system or a fitness apparatus.

[0034] A computer program product according to the invention comprises
instructions for causing a processor to carry out the steps of the method
as is set forth with reference to the foregoing.

[0035] These and other aspects of the invention will be discussed in
further detail with reference to drawings, wherein like reference signs
represent like numerals. It will be appreciated that the drawing are
provided for illustrative purposes and may not be used for limiting the
scope of the appended claims.

[0037] FIG. 2 presents schematically an embodiment of an adaptive pressure
transfer function in accordance with the invention.

[0038] FIG. 3 presents schematically an embodiment of a device according
to the invention.

DETAILED DESCRIPTION OF THE DRAWINGS

[0039] FIG. 1 presents schematically an embodiment of a generic pressure
transfer function. It will be appreciated that the pressure transfer
function 10 relates to a backward pressure transfer function, i.e. a
description of a blood pulse transfer from an extremity artery to the
aortic artery. In mathematical terms this is the inverse of the more
natural forward transfer function. An example of a suitable forward
pressure transfer function is known from Gizdulich et al "Models of
brachial to finger pulse wave distortion and pressure decrement",
Cardiovasc Res 33: 698-705, 1997, describing an amplitude transfer of a
pressure pulse from aorta to periphery. Accordingly, the transfer
function is expressed as follows:

[0045] FIG. 1 shows schematically a curve 1, representing a variation of
the gain of the pressure transfer function with frequency. It is seen
that there is a minimum value of the gain for intermediate frequencies at
Fpeak. Curve 2 schematically shows an averaged gain of a multiple
transfer functions. Such transfer functions may relate to ARX method,
described in Chen C H, Nevo E, Fetics B, Pak P H, Yin F C, Maughan W L
and Kass D A: "Estimation of central aortic pressure waveform by
mathematical transformation of radial tonometry pressure. Validation of
generalized transfer function", Circulation JID-0147763 95: 1827-1836,
1997.

[0046] In order to determine a suitable individualization of a generic
transfer function, blood pressure waveform data at rest and at the end of
an exercise step may be used. Such data may function as calibration data
for determining a suitable relation between an adjustable characteristics
of the pressure transfer function, for example the peak frequency
Fpeak and a pre-selected parameter, for example, cardiac output
derived from a suitable analysis of the pressure waveform, such as pulse
contour (pcCO), heart rate (HR), stroke volume (SV), total peripheral
resistance (TPR), pressure wave delay (Delay), peripheral mean arterial
pressure (MAP), diastolic arterial pressure (DBP). Preferably, several
heart beats of artefact-free continuous data are used for this purpose.
It will be appreciated that at least a minimum length of artefact-free
data may be one heart beat; and a maximum length of the artefact-free
continuous data may be several minutes.

[0047] An average ARX transfer function TF (curve 2 in FIG. 1) may be
determined from the resting data of a suitable plurality of subjects. A
transfer function TF described by two 2nd order filter sections,
known in the inverse form from Gizdulich et al "Models of brachial to
finger pulse wave distortion and pressure decrement", Cardiovasc Res 33:
698-705, 1997, may then be fitted to the frequency response of the
average ARX TF, resulting in a characteristic TF frequency response
(curve 1 in FIG. 1). This generalized filter (genTF) may be used as a
starting point for the individualization.

[0048] Based on regression analysis of plurality of patient data a formula
was developed that would adjust the frequency at which an individual
transfer function TF would peak (Fpeak). Preferably, the Gizdulich
filter is adapted to allow for a shift in the peak, which may be
implemented using a lookup table.

[0049] In order to apply this approach data used for the adjustment of the
individual TF peak frequency (Fpeak) may be taken from subject
parameters (age, length, weight, BSA), directly available from a
peripheral blood pressure wave signal (MAP, DBP, HR, dP/dt) or derived
using additional algorithms such as cardiac output derived from an
analysis of the pressure waveform, such as pulse contour (pcCO), stroke
volume (SV) and total peripheral resistance (TPR). Additionally, pressure
wave delay may be incorporated, as this parameter can also be measured
non-invasively and is a direct indicator of a change in wave
transmission.

[0050] It is found that pulse contour cardiac output (pcCO) is a most
reliable adjustor for adjusting the peak frequency of the pressure
transfer function, particularly during exercise, having a correlation
coefficient R2=0.86. Correlation coefficients for other pre-selected
parameters HR, dP/dt, SV, TPR, delay, estimated PWV, MAP, DBP being 0.71,
0.69, 0.63, 0.63, 0.56, 0.56, 0.51 and 0.35 respectively, may be somewhat
lower, but still acceptable.

[0051] The regression formula for adjustment of the frequency of the peak
in the TF from pcCO only may be as follows:

Fpeak=0.3206*pcCO+2.6784

[0052] Multivariate stepwise regression models constructed with the TF
peak frequency as the dependent variable resulted in further regression
formulas, with and without pressure wave delay as parameter:

Fpeak=0.0701*(MAP-DBP)+0.0193*HR-0.131*Delay+2.7067

Fpeak=0.0764*(MAP-DBP)+0.0234*HR+0.6478.

[0053] In accordance with the invention a simple and reliable method is
provided for accurately adjusting characteristics of a pressure transfer
function for reconstructing aortic blood pressure waveform from a
peripheral measurement with an improved accuracy.

[0054] FIG. 2 presents schematically an embodiment of an adaptive pressure
transfer function in accordance with the invention. The adaptive pressure
transfer function 20, may be adjusted yielding actual functions 21, 22,
23 depending on an actual value of a pre-selected parameter, for example
cardiac output derived from an analysis of the pressure waveform, such as
pulse contour (pcCO). It is seen than for different cardiac outputs, for
example during rest or during exercise, different values of the peak
frequency F1, F2, F3 of a filter gain are obtained. By applying the thus
adjusted pressure transfer function to the peripheral blood pressure
waveform aortic blood pressure waveform with improved accuracy may be
calculated.

[0055] FIG. 3 presents schematically an embodiment of a device according
to the invention. The device 30 according to the invention comprises a
suitable housing 31 comprising an input 36, a processing unit 34 a memory
unit 32 and a display 35. The memory unit 32 may be arranged for storing
a pressure transfer function 32a having at least one adjustable
characteristics and at least a peripheral blood pressure waveform 32b.
The processor 34 is preferably arranged for determining at least one
pre-selected parameter of the peripheral blood pressure waveform, for
determining the adjustable parameter of the pressure transfer function
from the at least one pre-selected parameter of the peripheral blood
pressure waveform and for reconstructing of aortic blood pressure
waveform from a peripheral blood pressure using the pressure transfer
function with the adjusted characteristics. For this purpose the memory
unit may comprise a computer program 32c arranged for causing the
processor 34 to carry out the method of the invention as is described
with reference to the foregoing.

[0056] Preferably, the device 30 further comprises a measurement unit 38
arranged to measure the peripheral blood pressure waveform, which may
relate to either invasive or a non-invasive measuring system. An
embodiment of an applicable non-invasive measuring system comprising a
finger cuff is known from U.S. Pat. No. 4,726,382. The finger cuff may
comprise an inflatable bladder formed from a thin flexible, translucent
material. The inflatable bladder may be connected to a tube enabling a
suitable inflation and deflation of the inflatable bladder. In the finger
cuff the inflatable bladder may be the innermost component of the cuff.
In order to implement a blood pressure measurement, the finger cuff may
comprise a photoplethysmograph.

[0057] It will be appreciated that device 30 according to the invention
may be arranged to carry out determination of arterial blood pressure
waveform on-line. In this case the input 36 may be arranged to receive
date (raw or pre-processed) from the measurement unit 38 and to calculate
the corresponding aortic blood pressure wave using adjusted pressure
transfer function, as described in the foregoing. Display 35 may be
arranged to display the measured peripheral blood pressure waveform and
the resulting reconstructed aortic blood pressure waveform. Additionally
or alternatively, the device 30 may be arranged to continuously measure
peripheral blood pressure, eventually out of phase, and to present a
corresponding derived arterial blood pressure on the display 35. The
arterial blood pressure may be presented as a value. Additionally or
alternatively the arterial blood pressure may be presented graphically,
for example as a function of time. In an embodiment, such graphic
representation may relate to a line indicating a trend in the measured
arterial blood pressure.

[0058] Alternatively, the device 30 may be arranged to carry out
reconstruction of the aortic blood pressure waveform off-line. In this
case the input 36 may be arranged to receive suitable data on peripheral
blood pressure waveform from a suitable source, like a data carrier, or
via intranet or internet.

[0059] In a particular embodiment of the device 30 according to the
invention, the processor 34 may be arranged to calculate a suitable
health-related parameter from the reconstructed aortic pressure waveform
data. Preferably, the device 30 forms part of a suitable fitness
equipment or a suitable monitoring equipment. More preferable, the
calculated health-related parameter is automatically analyzed and a
suitable advice to the person is forwarded. The advice may comprise a
life style advice, a fitness program advice, or a medical advice. In a
particular embodiment the medical advice may relate to a warning or to an
advice regarding an increased health hazard leading to a suitable further
medical diagnostic advice. In acute circumstances, for example, when the
health related parameter signals an impending cardiac overload, the
device 30 may be arranged to automatically forward a suitable alarm to
dispatch immediate attention of medical personnel. For example a call to
a heart alert call center may be automatically realized. This
functionality improves para-medical applicability of the device 30
according to the invention.

[0060] While specific embodiments have been described above, it will be
appreciated that the invention may be practiced otherwise than as
described. The descriptions above are intended to be illustrative, not
limiting. Thus, it will be apparent to one skilled in the art that
modifications may be made to the invention as described in the foregoing
without departing from the scope of the claims set out below.